Retinoids are new drugs that can be used in the prevention of cancer of epithelial tissues. Since the tissue distribution and disposition of the synthetic members of this class of compounds is essentially unknown, we propose to determine, by a sensitive procedure involving high-pressure liquid chromatography (HPLC), the blood levels and tissue distribution of 13-cis-retinoic acid, retinyl methyl ether, and N-2-hydroxyenthylretinamide in mice following oral and intravenous injections. All-trans-retinoic acid will be included as a control. Our HPLC procedure uniquely allows determination of a variety of retinoids in a variety of animal tissues. For these four retinoids, we also propose to determine (a) the effect of inducers of mixed-function oxidases on their disposition in rats, (b) their subcellular distribution in responsive tissues, and (c) whether or not they accumulate in the livers of mice. The experiments are designed to elucidate any relationship between distribution of retinoids and their therapeutic effect. Such a relationship would be helpful in selection of the most appropriate retinoids for prevention of cancer in man.